Obesity and weight regulation are increasingly prominent topics in the discourse on health in the United States. Obesity now affects over one-third of American adults at great personal and public cost. Despite widespread attention to obesity as a public health crisis, effective treatments for this disease remain limited. Because obesity is so heavily impacted by the current food environment that promotes easy access to calorie-dense meals, effective strategies to reduce weight will likely need to include behavioral modification (i.e. diet and exercise). Consequently, improved understanding of the neural circuitry involved in driving food intake is necessary for systematic treatment of this disease. The research proposed here aims to dissect the circuitry involved in motivational drive as it relates to food intake. Specific Aims: The Nucleus Accumbens (NAc) is a central circuit in the regulation of food intake. While much study has focused on regions of the NAc, there is a lack of understanding of the direct relationship between activity of discrete populations of neurons within the NAc and behavioral output. Recent advances in technology of optogenetics, electrophysiology and genetic manipulation, allow more focused study on these subpopulations. Aim 1 explores the native activity of dopamine receptor 2 (D2R)-expressing NAc projection neurons (MSNs), during food intake. Aim 2 examines the relationship between changes in activity of these neurons and changes in food intake behavior. Aim 3 manipulates the D2 receptor to discover its contribution to the normal behavior directed by these neurons. Impact: The ability to accurately describe the relationship between the D2-neuron and intake behavior will allow sophisticated design of pharmaceutical therapies and may open avenues to new therapeutic options. Recently, brain imaging modalities such as fMRI have been combined with biofeedback to allow patients to retrain their responses to the environment. Such interventions have demonstrated benefit in treatment of anxiety and addiction. Obesity and weight regulation may represent appropriate targets for these therapies once neuronal activity underlying this disease is better characterized.